The WHI study worked on the assumption that one dose would fit all asymptomatic
post menopausal women. The investigators therefore often used
the wrong dose, of the wrong hormones on the wrong patients and therefore
came to many wrong conclusions. Different combinations of different
hormones are necessary for different symptoms and different age groups. HRT
may be commenced in the peri-menopausal phase, the early post menopause,
the late post menopause or after hysterectomy and bilateral salpingo-oophorectomy
or a premature menopause. These all require different treatments. Similarly
various indications such as vasomotor symptoms, sexual problems, depression
or the treatment/prevention of osteoporosis all need different combinations
of oestradiol and possibly progestogen and testosterone according to
the specific requirements of the patient.

Introduction

Two major well publicised studies, the Women’s Health Initiative
(WHI) (1) and the Million Women Study (MWS) (2) has shaken the faith
in the safety of HRT for doctors and post menopausal women alike in spite
of the criticism of the design and conclusions of the WHI study (3-5)
and the many anxieties about the MWS data collection. (6-8) It is now
difficult to respond to the WHI study in an optimistic way and for this
to be considered and published. Following the NAMS/NIH statement
of October 2002 (9) many proscriptive guidelines from advisory bodies
in Europe and North America have appeared, which advise prescribing hormone
therapy at the lowest dose principally for menopausal vasomotor symptoms,
and for the shortest time. (10) It was also recommended that it was not
to be used as a primary treatment for low bone density and that it has
no place in the prevention of coronary heart disease. In view of later
consideration of the data both items of advice are questionable. There
is no protest about the uncontroversial recommendation that the lowest
dose should be used and the appropriateness of continuing HRT should
be reviewed each year with full discussion of benefits and risks. However
the ‘lowest dose’ varies from patient to patient and should
be one that is effective for a particular indication.

What is missing from statements from regulatory authorities is the understanding
that treatment should be individualised for a particular patient, her
expectations and her pathology. Such variation of therapy is sound clinical
practice but it is notable that the great fault of the WHI study
is that there was no individualisation with the assumption that
one dose of Prempro fitted all patients regardless of age and general
health even though they were, by their inclusion criteria, asymptomatic
and did not require therapy.

The epidemiologists and investigators who designed the WHI were not
aware, or chose to ignore the basic tenant of good practice relating
to HRT. This is the knowledge that different women, require a different
dose, by a different route, of different combinations, of different hormones,
for different symptoms. This would also vary depending upon the
surgical status, the age of the patient and there will also be a difference
depending on the clinical needs of the woman. This paper is an attempt
to correct that omission by stating the variations necessary for effective
treatment with estrogens with the possible addition of progestogens
and androgens..